The purpose of the proposed research project is: (1) to obtain information about the structures and catalytic mechanisms of dihydrofolate reductase and methionine synthetase; (2) to obtain information about the transport of folate compounds (particularly folate 5-methyl tetrahydrofolate, and amethopterin) and vitamin B12 into cells; and (3) to utilize the above information in the design of new cancer chemotherapeutic regimens.